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Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells.

Fahey AJ, Adrian Robins R, Constantinescu CS - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta.Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation.Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurology, University of Nottingham, Nottingham, UK.

ABSTRACT
Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

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Modulation of IL-12 by curcumin. Quantitative real-time PCR was used to assess IL-12 mRNA expression in PHA/IL-2 T cell blasts. Prior exposure to IL-12 (100 ng/ml) alone up-regulated both IL-12 Rβ1 and β2 expression. This induction, however, was reduced following pre-exposure to curcumin (20 μg/ml). β2microglobulin expression was monitored as an internal standard on the cDNA template; mRNA expression for each gene is normalized to the internal standard expression. US = unstimulated.
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fig03: Modulation of IL-12 by curcumin. Quantitative real-time PCR was used to assess IL-12 mRNA expression in PHA/IL-2 T cell blasts. Prior exposure to IL-12 (100 ng/ml) alone up-regulated both IL-12 Rβ1 and β2 expression. This induction, however, was reduced following pre-exposure to curcumin (20 μg/ml). β2microglobulin expression was monitored as an internal standard on the cDNA template; mRNA expression for each gene is normalized to the internal standard expression. US = unstimulated.

Mentions: We next investigated whether curcumin also exerted its effects upstream at the receptor level. Quantitative real-time PCR was used to assess IL-12R and IFNAR mRNA expression in PHA/IL-2 T cell blasts. Both IFN-β and IFN-α modestly increased IFNAR1 expression; this was further increased by prior exposure to curcumin (P < 0.05). Prior exposure to cur-cumin also induced a moderate increase of IFNAR2 by IFN-β (Fig. 2). However, although IFN-α alone increased IFNAR2 expression, prior exposure to cur-cumin had no effect on IFN-α-induced IFNAR2 expression. In this study, prior exposure to IL-12 alone up-regulated both IL-12 Rβ1 and β2 expression (Fig. 3). However, pre-exposure to curcumin appeared to reduce this induction (Fig. 3, IL-12Rβ1 P= 0.074, IL-12Rβ2 P < 0.05). Similar results were also obtained when measuring IL-12Rβ1 and IFNAR protein expression using flow cytomtery. The median fluorescence intensity (MFI) for IFNAR was increased from 5.4 (range, 5.4–11.2) to 11.12 (10.35–15.5) when comparing unstimulated cells with cells incubated with IFN-β, respectively. Pretreatment with curcumin followed by IFN-β enhanced the MFI of IFNAR to 18.47 (11.2–28.0). Exposure to IL-12 alone increased β1 receptor whilst pre-exposure to curcumin decreased the IL-12 receptor β1 expression. The MFI was increased from 16.5 (9–28) to 29.0 (25.5–40) when comparing unstimulated cells with cells incubated with IL-12, respectively. Pretreatment with curcumin reduced the MFI of IL-12Rβ 1 to 21.5 (19–31). These medians (range) are from three independent experiments. All these differences above were statistically significant (P < 0.05).


Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells.

Fahey AJ, Adrian Robins R, Constantinescu CS - J. Cell. Mol. Med. (2007 Sep-Oct)

Modulation of IL-12 by curcumin. Quantitative real-time PCR was used to assess IL-12 mRNA expression in PHA/IL-2 T cell blasts. Prior exposure to IL-12 (100 ng/ml) alone up-regulated both IL-12 Rβ1 and β2 expression. This induction, however, was reduced following pre-exposure to curcumin (20 μg/ml). β2microglobulin expression was monitored as an internal standard on the cDNA template; mRNA expression for each gene is normalized to the internal standard expression. US = unstimulated.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401279&req=5

fig03: Modulation of IL-12 by curcumin. Quantitative real-time PCR was used to assess IL-12 mRNA expression in PHA/IL-2 T cell blasts. Prior exposure to IL-12 (100 ng/ml) alone up-regulated both IL-12 Rβ1 and β2 expression. This induction, however, was reduced following pre-exposure to curcumin (20 μg/ml). β2microglobulin expression was monitored as an internal standard on the cDNA template; mRNA expression for each gene is normalized to the internal standard expression. US = unstimulated.
Mentions: We next investigated whether curcumin also exerted its effects upstream at the receptor level. Quantitative real-time PCR was used to assess IL-12R and IFNAR mRNA expression in PHA/IL-2 T cell blasts. Both IFN-β and IFN-α modestly increased IFNAR1 expression; this was further increased by prior exposure to curcumin (P < 0.05). Prior exposure to cur-cumin also induced a moderate increase of IFNAR2 by IFN-β (Fig. 2). However, although IFN-α alone increased IFNAR2 expression, prior exposure to cur-cumin had no effect on IFN-α-induced IFNAR2 expression. In this study, prior exposure to IL-12 alone up-regulated both IL-12 Rβ1 and β2 expression (Fig. 3). However, pre-exposure to curcumin appeared to reduce this induction (Fig. 3, IL-12Rβ1 P= 0.074, IL-12Rβ2 P < 0.05). Similar results were also obtained when measuring IL-12Rβ1 and IFNAR protein expression using flow cytomtery. The median fluorescence intensity (MFI) for IFNAR was increased from 5.4 (range, 5.4–11.2) to 11.12 (10.35–15.5) when comparing unstimulated cells with cells incubated with IFN-β, respectively. Pretreatment with curcumin followed by IFN-β enhanced the MFI of IFNAR to 18.47 (11.2–28.0). Exposure to IL-12 alone increased β1 receptor whilst pre-exposure to curcumin decreased the IL-12 receptor β1 expression. The MFI was increased from 16.5 (9–28) to 29.0 (25.5–40) when comparing unstimulated cells with cells incubated with IL-12, respectively. Pretreatment with curcumin reduced the MFI of IL-12Rβ 1 to 21.5 (19–31). These medians (range) are from three independent experiments. All these differences above were statistically significant (P < 0.05).

Bottom Line: Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta.Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation.Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Neurology, University of Nottingham, Nottingham, UK.

ABSTRACT
Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

Show MeSH
Related in: MedlinePlus